Analysis of brain metabolites by gas chromatography–mass spectrometry reveals the risk–benefit concerns of prednisone in MRL/lpr lupus mice
Analysis of brain metabolites by gas chromatography–mass spectrometry reveals the risk–benefit concerns of prednisone in MRL/lpr lupus mice
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通过气相色谱-质谱分析脑代谢物揭示了 MRL/lpr 狼疮小鼠中泼尼松的风险与益处问题
DOI：
10.1007/s10787-019-00668-4
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发表时间：
2020
影响因子：
5.8
通讯作者：
Zhenghao Xu
中科院分区：
文献类型：
--
作者：
Jia Zhou;Feilong Lu;Shan Li;Meijuan Xie;Haimei Lu;Zhijun Xie;Dehong Wu;Shuang Wang;Chengping Wen;Zhenghao Xu
目的神经精神性系统性红斑狼疮(NPSLE)是系统性红斑狼疮(SLE)致残的常见原因。本研究旨在探讨狼疮易感小鼠下丘脑和额叶皮质的代谢变化。方法用气相色谱-质谱仪(GC-MS)分析其代谢变化。结果主成分分析(PCA)显示，MRL/LPR和MRL/MPJ小鼠(16周龄)在额叶和下丘脑中的代谢变化不同，但两者之间的代谢规律是相似的。与MRL/MPJ小鼠相比，OPLS-DA法鉴定出MRL/LPR小鼠的8种大脑皮层和6种下丘脑差异代谢物。在这些差异代谢物中，我们发现在额叶皮质中N-乙酰-L-天冬氨酸减少，丙酮酸增加，谷氨酸减少，而在下丘脑中则没有。8周龄起给予泼尼松(3 mg/kg)治疗后，额叶皮质NAA含量下降，丙酮酸蓄积进一步增加，下丘脑8条通路受累，导致额叶皮质和下丘脑兴奋与抑制明显失衡。结论SLE患者额叶皮质较下丘脑优先受累。泼尼松破坏而非缓解了脑内的代谢异常，尤其是下丘脑的代谢异常，表明强的松对SLE或NPSLE的风险-收益平衡仍有待进一步评估。
ObjectiveNeuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice.MethodsMetabolic changes were analyzed using gas chromatography-mass spectrometry (GC–MS).ResultsAccording to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease ofN-acetyl-l-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus.ConclusionThese results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk–benefit balance of prednisone for SLE or NPSLE remains to be further evaluated.